1 Intermountain Healthcare Clinical Genetics Institute Marc S. Williams, M.D. Director Grant M. Wood Senior IT Strategist Introduction to HL7 Clinical

1

Intermountain Healthcare Clinical Genetics Institute Marc S. Williams, M.D.

DirectorGrant M. Wood

Senior IT Strategist

Introduction to HL7 Clinical Genomics

2

Informatics Line in our Brochure

• Link genomic/family medical history data to the electronic medical record to provide advanced genetics-based tools for the clinician.

3

Genomics and Informatics

• Clinical genomics data could dwarf the data

storage and management challenges posed

by genome sequencing projects.

• Personalized medicine will require an

increased integration of clinical and research

databases.

4

Health Level Seven (HL7) Overview

• HL7 is an international community of healthcare clinical and informatics experts collaborating to create standards of electronic healthcare information

• The organization is comprised of Technical Committees (like Clinical Decision Support, Electronic Health Records, Medical Records, etc) and Special Interest Groups (like Clinical Genomics)

• Develop standards that permit structured, encoded health care information, to be exchanged between computer applications

• Collaborate with other standards development organizations • Encourage organizations to participate in HL7 to develop healthcare

information standards in their area of expertise • Collaborate with healthcare information technology users to ensure that

HL7 standards meet real-world requirements

5

HL7 Clinical Genomics

• Lead model developer is Amnon Shabo from the IBM Haifa Research Lab

•Other participants include representatives from healthcare provider, pharmaceutical, software vendor, professional services, and Veterans Administration

•Genetic Locus, Genetic Loci, and Family History models approved via ballot as Draft Standard for Trial Use

•Model is designed to store genomic data in the EHR for use by clinical decision support applications

•Waiting for implementation by early adopters and partners to test the exchange of clinical genomic and family history data

6

0..* associatedObservation

typeCode*: <= COMP

component

0..* associatedProperty

typeCode*: <= DRIV

derivedFrom2

0..* polypeptide

typeCode*: <= DRIV

derivedFrom5

SEQUENCES & PROTEOMICS

0..* expression

typeCode*: <= COMPcomponent1

0..* sequenceVariation

typeCode*: <= COMP

component3

IndividualAlleleclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]negationInd: BL [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: CD [0..1] (allele code, drawn from HUGO-HGVS or OMIM)methodCode: SET<CE> CWE [0..*]

GeneticLocusclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CE CWE [0..1] (e.g., ALLELIC, NON_ALLELIC)text: ED [0..1]effectiveTime: IVL<TS> [0..1]confidentialityCode: SET<CE> CWE [0..*] <= ConfidentialityuncertaintyCode: CE CNE [0..1] <= Uncertaintyvalue: CD [0..1] (identifying a gene through GenBank GeneID with an optional translation to HUGO name.)methodCode: SET<CE> CWE [0..*]

0..* individualAllele

typeCode*: <= COMP

component1

SequenceclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CD CWE [1..1] (the sequence standard code, e.g. BSML)text: ED [0..1] (sequence's annotations)effectiveTime: GTS [0..1]uncertaintyCode: CE CNE [0..1] <= Uncertaintyvalue: ED [1..1] (the actual sequence)interpretationCode: SET<CE> CWE [0..*] <= ObservationInterpretationmethodCode: SET<CE> CWE [0..*] (the sequencing method)

ExpressionclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CE CWE [1..1] (the standard's code (e.g., MAGE-ML identifier)negationInd: BL [0..1]text: ED [0..1]effectiveTime: GTS [0..1]uncertaintyCode: CE CNE [0..1] <= Uncertaintyvalue: ED [1..1] (the actual gene or protein expression levels)interpretationCode: SET<CE> CWE [0..*] <= ObservationInterpretationmethodCode: SET<CE> CWE [0..*]

PolypeptideclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: CD [0..1] (protein code, drawn from SwissProt, PDB, PIR,HUPO, etc.)methodCode: SET<CE> CWE [0..*]

DeterminantPeptidesclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: CD [0..1] (peptide code, drawn from referencedatabases like those used in the Polypeptide class)methodCode: SET<CE> CWE [0..*]

Constrained to a restrictedMAGE-ML constrained schema,specified separately.

Constraint: GeneExpression.value

Note:A related allele that is ona different locus, and hasinterrelation with thesource allele, e.g.,translocated duplicatesof the gene.

0..* clinicalPhenotype

typeCode*: <= PERTpertinentInformation

ExternalObservedClinicalPhenotypeclassCode*: <= OBSmoodCode*: <= EVNid*: II [1..1] (The unique id of an external observation residing outside of the instance)code: CD CWE [0..1]text: ED [0..1]effectiveTime: GTS [0..1]

Note:An external observation is preferably a valid observationinstance existing in any other HL7-compliant instance,e.g., a document or a message.Use the id attribute of this class to point to the uniqueinstance identifier of that observation.

Note:A phenotype which has been actuallyobserved in the patient representedinternally in this model.

Note:This is a computed outcome, i.e.,the lab does not test for the actualprotein, but secondary processespopulate this class with thetranslational protein.

SequenceVariationclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CD CWE [0..1]negationInd: BL [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: ANY [0..1] (The variation itself expressed with recognized notation like 269T>C or markup like BSML or drawn from an external reference like OMIM or dbSNP.)interpretationCode: SET<CE> CWE [0..*] <= ObservationInterpretationmethodCode: SET<CE> CWE [0..*]

KnownClinicalPhenotypeclassCode*: <= OBSmoodCode*: <= DEFcode: CD CWE [0..1]text: ED [0..1]effectiveTime: GTS [0..1]uncertaintyCode: CE CNE [0..1] <= ActUncertaintyvalue: ANY [0..1]

Note:These phenotypes are not the actual (observed)phenotypes for the patient, rather they are thescientifically known phenotypes of the sourcegenomic observation (e.g., known risks of amutation or know responsiveness to a medication).

Note:Code: COPY_NUMBER, ZYGOSITY, DOMINANCY, GENE_FAMILY,etc. For example, if code = COPY_NUMBER, then the value is oftype INT and is holding the no. of copies of this gene or allele.


typeCode*: <= PERT

pertinentInformation

EXPRESSION DATA

SEQUENCE VARIATIONS

Polypeptide

Note:The Expression class refers to both gene and proteinexpression levels. It is an encapsulating class that allowsthe encapsulation of raw expression data in its value attribute.

0..* sequence


0..* clinicalPhenotypetypeCode*: <= PERT



typeCode*: <= PERT


Note:The code attribute indicates inwhat molecule the variation occurs,i.e., DNA, RNA or Protein.

0..* expression

typeCode*: <= COMP

component5

Note:Use the associations to the shadowclasses when the data set type (e.g.,expression) is not at deeper levels(e.g., allelic level) and needs to beassociated directly with the locus(e.g., the expression level is thetranslational result of both alleles).

0..* associatedObservationtypeCode*: <= COMP

component2

0..1 associatedObservation

typeCode*: <= COMP

component4 Note:This recursive associationenables the association of anRNA sequence derived froma DNA sequence and apolypeptide sequence derivedfrom the RNA sequence.


typeCode*: <= PERT


Note:

This class is a placeholder for a specific locus on the genome - that is - a position of a particulargiven sequence in the subject’s genome or linkage map.Note that the semantics of the locus (e.g., gene, marker, variation, etc.) is defined by data assignedin the code & value attributes of this class, and also by placing additional data relating to thislocus into the classes associated with this class like Sequence, Expression, etc..

Note:The term 'Individual Allele' doesn't refer necessarily to aknown variant of the gene/locus, rather it refers to theindividual patient data regarding the gene/locus and mightwell contain personal variations w/unknown significance.

AssociatedObservationclassCode*: <= OBSmoodCode*: <= EVNid: SET<II> [0..*]code: CD CWE [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: ANY [0..1]methodCode: SET<CE> CWE [0..*]

Note:The code attribute could hold codes likeNORMALIZED_INTENSITY, P_VALUE, etc.The value attribute is populated based on theselected code and its data type is then setupaccordingly during instance creation.

Note:The code attribute could hold codes like TYPE,POSITION.GENOME, LENGTH, REFERENCE, REGION, etc..The value attribute is populated based on the selected codeand its data type is then setup accordingly during instancecreation. Here are a few examples:If code = TYPE, then the value is of type CV and holds one of thefollowing: SNP (tagSNP), INSERTION, DELETION,TRANSLOCATION, etc.

if code = POSITION, then value is of type INT and holdsthe actual numeric value representing the variation positionalong the gene.

if code = LENGTH, then value is of type INT and holdsthe actual numeric value representing the variation length.

If code = POSITION.GENE, then value is of type CV and is oneof the following codes:INTRON, EXON, UTR, PROMOTER, etc.

If code = POSITION.GENOME, then value is of type CV and is oneof the following codes:NORMAL_LOCUS, ECTOPIC, TRANSLOCATION, etc.

If the code = REFERENCE, then value istype CD and holds the reference gene identifier drawn from areference database like GenBank.

The full description of the allowed vocabularies for codes and itsrespective values could be found in the specification.

AssociatedObservation

Note:Code: CLASSIFICATION, etc.For example, if code =CLASSIFICATION, then the valueis of type CV and is holding eitherKNOWN or NOVEL.

reference

0..* geneticLocus

typeCode*: <= REFR

Note:A related gene that is on adifferent locus, and stillhas significant interrelationwith the source gene (similarto the recursive associationof an IndividualAllele).

ClinicalPhenotypeclassCode*: <= ORGANIZERmoodCode*: <= EVN

0..* observedClinicalPhenotype

typeCode*: <= COMP

component1

0..* knownClinicalPhenotype

typeCode*: <= COMP

component2

0..* externalObservedClinicalPhenotype

typeCode*: <= COMP

component3

At least one of the target acts ofthe three component act relationshipsshould be populated, since this isjust a wrapper class.

Constraint: ClinicalPhenotype

Note:- code should indicate the type of source, e.g., OMIM- text could contain pieces from research papers- value could contain a phenotype code if known (e.g., if it’s a disease, then the disease code)

ClinicalPhenotype

ClinicalPhenotype

ClinicalPhenotype

ClinicalPhenotype

ClinicalPhenotype

ClinicalPhenotype

0..1 identifiedEntity

typeCode*: <= SBJcontextControlCode: CS CNE [0..1] <= ContextControl "OP"

subject

reference


typeCode*: <= REFR

ObservedClinicalPhenotype

Note:This CMET might be replacedwith the Clinical Statement SharedModel for richer expressivity, whenthe that mode is approved(currently in ballot).

Constrained to a restricted BSMLcontent model, specified in aseparate schema.

Constraint: Sequence.value

0..* sequence

typeCode*: <= COMP

component4


typeCode*: <= COMP

component3

AssociatedPropertyclassCode*: <= OBSmoodCode*: <= EVNcode: CD CWE [0..1]text: ED [0..1]value: ANY [0..1]


typeCode*: <= DRIVderivedFrom1



typeCode*: <= COMP

component

AssociatedPropertyAssociatedObservation


typeCode*: <= DRIV

derivedFrom

AssociatedProperty0..* associatedProperty


AssociatedObservation0..* associatedObservation

typeCode*: <= COMPcomponent

0..* sequenceVariationtypeCode*: <= DRIV

derivedFrom3derivedFrom2

0..* sequence

typeCode*: <= DRIV

0..* determinantPeptides

typeCode*: <= DRIV

derivedFrom4


typeCode*: <= DRIVderivedFrom


typeCode*: <= PERT

pertinentInformation 0..* clinicalPhenotype

typeCode*: <= PERT


AssociatedProperty


typeCode*: <= DRIV

derivedFrom

AssociatedProperty

GeneticLociclassCode*: <= OBSmoodCode*: <= EVNid: SET<II> [0..*]code: CD CWE [0..1]effectiveTime: GTS [0..1]value: ANY [0..1]

0..* geneticLocitypeCode*: <= COMPcomponentOf



GeneticLoci

0..* geneticLoci

typeCode*: <= COMP

componentOf

GeneticLoci

0..* geneticLoci

typeCode*: <= COMP

componentOf

0..* polypeptide


Polypeptide

0..* polypeptide

typeCode*: <= DRIV

derivedFrom2

Note:Use this class to indicate a set of genetic locito which this locus belongs. The loci set couldbe a haplotype, a genetic profile and so forth.Use the id attribute to point to the GeneticLociinstance if available. The other attributesserve as a minimal data set about the loci group.

PHENOTYPES

Note:Any observation related to the variation and is notan inherent part of the variation observation (the lattershould be represented in the AssociatedProperty class).For example, the zygosity of the variation.

Note:Use this class to point to a variationgroup to which this variation belongs.For example, a SNP haplotype.

Note:Any observation related to the sequence and is notan inherent part of the sequence observation (the lattershould be represented in the AssociatedProperty class).For example, splicing alternatives.

Note:Key peptides in the proteinthat determine its function.

Note:There could be zero to manyIndividualAllele objects in aspecific instance. A typicalcase would be an allele pair,one on the paternalchromosome and one on thematernal chromosome.

Note:Use this class toshow an allelehaplotype like in HLA.

Note:Any observationrelated to theexpression assayand is not aninherent part ofthe expressionobservation.

Note:Use this class forinherent dataabout the locus, e.g.chromosome no.

IdentifiedEntityclassCode*: <= IDENTid: SET<II> [0..*]code: CE CWE [0..1] <= RoleCode

Note:Use this role to identify a different subject(e.g., healthy tissue, virus, etc.) than theone propagated from the wrappingmessage or payload (e.g., GeneticLoci).

ScopingEntityclassCode*: <= LIVdeterminerCode*: <= INSTANCEid: SET<II> [0..*]code: CE CWE [0..1] <= EntityCode

0..* assignedEntity

typeCode*: <= PRFcontextControlCode: CS CNE [0..1] <= ContextControl "OP"

performer

0..*

performer

0..*

performer1

0..*

performer2

0..*

performer1

0..*

performer2

Genetic Locus(POCG_RM000010)

The entry point tothe GeneticLocus modelis any locus on the genome.

Constrained to a restricted MAGE-MLcontent model, specified in aseparate schema.

Constraint: Expression.value

Expression

Sequence

SequenceVariation

SequenceVariation



ClinicalPhenotype

CMET: (ASSIGNED) R_AssignedEntity

[universal](COCT_MT090000)

0..1 scopedRoleName

CMET: (ACT) A_SupportingClinicalInformation


The Locus

and its Alleles

Sequence

Variations

Expression

Data

Sequence

and

Proteomics

Clinical

Phenotypes

The GeneticLocus Model - Focal Areas:

7

Incorporation of CG data into the EHR


typeCode*: <= COMP

component


typeCode*: <= DRIV

derivedFrom2

0..* polypeptide


SEQUENCES & PROTEOMICS

0..* expression



typeCode*: <= COMP

component3

IndividualAlleleclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]negationInd: BL [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: CD [0..1] (allele code, drawn from HUGO-HGVS or OMIM)methodCode: SET<CE> CWE [0..*]

GeneticLocusclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CE CWE [0..1] (e.g., ALLELIC, NON_ALLELIC)text: ED [0..1]effectiveTime: IVL<TS> [0..1]confidentialityCode: SET<CE> CWE [0..*] <= ConfidentialityuncertaintyCode: CE CNE [0..1] <= Uncertaintyvalue: CD [0..1] (identifying a gene through GenBank GeneID with an optional translation to HUGO name.)methodCode: SET<CE> CWE [0..*]



SequenceclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CD CWE [1..1] (the sequence standard code, e.g. BSML)text: ED [0..1] (sequence's annotations)effectiveTime: GTS [0..1]uncertaintyCode: CE CNE [0..1] <= Uncertaintyvalue: ED [1..1] (the actual sequence)interpretationCode: SET<CE> CWE [0..*] <= ObservationInterpretationmethodCode: SET<CE> CWE [0..*] (the sequencing method)

ExpressionclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CE CWE [1..1] (the standard's code (e.g., MAGE-ML identifier)negationInd: BL [0..1]text: ED [0..1]effectiveTime: GTS [0..1]uncertaintyCode: CE CNE [0..1] <= Uncertaintyvalue: ED [1..1] (the actual gene or protein expression levels)interpretationCode: SET<CE> CWE [0..*] <= ObservationInterpretationmethodCode: SET<CE> CWE [0..*]

PolypeptideclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: CD [0..1] (protein code, drawn from SwissProt, PDB, PIR,HUPO, etc.)methodCode: SET<CE> CWE [0..*]

DeterminantPeptidesclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: CD [0..1] (peptide code, drawn from referencedatabases like those used in the Polypeptide class)methodCode: SET<CE> CWE [0..*]

Constrained to a restrictedMAGE-ML constrained schema,specified separately.

Constraint: GeneExpression.value

Note:A related allele that is ona different locus, and hasinterrelation with thesource allele, e.g.,translocated duplicatesof the gene.



ExternalObservedClinicalPhenotypeclassCode*: <= OBSmoodCode*: <= EVNid*: II [1..1] (The unique id of an external observation residing outside of the instance)code: CD CWE [0..1]text: ED [0..1]effectiveTime: GTS [0..1]

Note:An external observation is preferably a valid observationinstance existing in any other HL7-compliant instance,e.g., a document or a message.Use the id attribute of this class to point to the uniqueinstance identifier of that observation.

Note:A phenotype which has been actuallyobserved in the patient representedinternally in this model.

Note:This is a computed outcome, i.e.,the lab does not test for the actualprotein, but secondary processespopulate this class with thetranslational protein.

SequenceVariationclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CD CWE [0..1]negationInd: BL [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: ANY [0..1] (The variation itself expressed with recognized notation like 269T>C or markup like BSML or drawn from an external reference like OMIM or dbSNP.)interpretationCode: SET<CE> CWE [0..*] <= ObservationInterpretationmethodCode: SET<CE> CWE [0..*]

KnownClinicalPhenotypeclassCode*: <= OBSmoodCode*: <= DEFcode: CD CWE [0..1]text: ED [0..1]effectiveTime: GTS [0..1]uncertaintyCode: CE CNE [0..1] <= ActUncertaintyvalue: ANY [0..1]

Note:These phenotypes are not the actual (observed)phenotypes for the patient, rather they are thescientifically known phenotypes of the sourcegenomic observation (e.g., known risks of amutation or know responsiveness to a medication).

Note:Code: COPY_NUMBER, ZYGOSITY, DOMINANCY, GENE_FAMILY,etc. For example, if code = COPY_NUMBER, then the value is oftype INT and is holding the no. of copies of this gene or allele.


typeCode*: <= PERT


EXPRESSION DATA

SEQUENCE VARIATIONS

Polypeptide

Note:The Expression class refers to both gene and proteinexpression levels. It is an encapsulating class that allowsthe encapsulation of raw expression data in its value attribute.

0..* sequence






Note:The code attribute indicates inwhat molecule the variation occurs,i.e., DNA, RNA or Protein.

0..* expression

typeCode*: <= COMP

component5

Note:Use the associations to the shadowclasses when the data set type (e.g.,expression) is not at deeper levels(e.g., allelic level) and needs to beassociated directly with the locus(e.g., the expression level is thetranslational result of both alleles).

0..* associatedObservationtypeCode*: <= COMPcomponent2

0..1 associatedObservation

typeCode*: <= COMP

component4 Note:This recursive associationenables the association of anRNA sequence derived froma DNA sequence and apolypeptide sequence derivedfrom the RNA sequence.


typeCode*: <= PERT


Note:This class is a placeholder for a specific locus on the genome - that is - a position of a particulargiven sequence in the subject’s genome or linkage map.Note that the semantics of the locus (e.g., gene, marker, variation, etc.) is defined by data assignedin the code & value attributes of this class, and also by placing additional data relating to thislocus into the classes associated with this class like Sequence, Expression, etc. .

Note:The term 'Individual Allele' doesn't refer necessarily to aknown variant of the gene/locus, rather it refers to theindividual patient data regarding the gene/locus and mightwell contain personal variations w/unknown significance.

AssociatedObservationclassCode*: <= OBSmoodCode*: <= EVNid: SET<II> [0..*]code: CD CWE [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: ANY [0..1]methodCode: SET<CE> CWE [0..*]

Note:The code attribute could hold codes likeNORMALIZED_INTENSITY, P_VALUE, etc.The value attribute is populated based on theselected code and its data type is then setupaccordingly during instance creation.

Note:The code attribute could hold codes like TYPE,POSITION.GENOME, LENGTH, REFERENCE, REGION, etc..The value attribute is populated based on the selected codeand its data type is then setup accordingly during instancecreation. Here are a few examples:If code = TYPE, then the value is of type CV and holds one of thefollowing: SNP (tagSNP), INSERTION, DELETION,TRANSLOCATION, etc.

if code = POSITION, then value is of type INT and holdsthe actual numeric value representing the variation positionalong the gene.

if code = LENGTH, then value is of type INT and holdsthe actual numeric value representing the variation length.

If code = POSITION.GENE, then value is of type CV and is oneof the following codes:INTRON, EXON, UTR, PROMOTER, etc.

If code = POSITION.GENOME, then value is of type CV and is oneof the following codes:NORMAL_LOCUS, ECTOPIC, TRANSLOCATION, etc.

If the code = REFERENCE, then value istype CD and holds the reference gene identifier drawn from areference database like GenBank.

The full description of the allowed vocabularies for codes and itsrespective values could be found in the specification.


Note:Code: CLASSIFICATION, etc.For example, if code =CLASSIFICATION, then the valueis of type CV and is holding eitherKNOWN or NOVEL.

reference

0..* geneticLocus

typeCode*: <= REFR

Note:A related gene that is on adifferent locus, and stillhas significant interrelationwith the source gene (similarto the recursive associationof an IndividualAllele).

ClinicalPhenotypeclassCode*: <= ORGANIZERmoodCode*: <= EVN

0..* observedClinicalPhenotype

typeCode*: <= COMP

component1

0..* knownClinicalPhenotype

typeCode*: <= COMP

component2

0..* externalObservedClinicalPhenotype

typeCode*: <= COMP

component3

At least one of the target acts ofthe three component act relationshipsshould be populated, since this isjust a wrapper class.

Constraint: ClinicalPhenotype

Note:- code should indicate the type of source, e.g., OMIM- text could contain pieces from research papers- value could contain a phenotype code if known (e.g., if it’s a disease, then the disease code)

ClinicalPhenotype

ClinicalPhenotype

ClinicalPhenotype

ClinicalPhenotype

ClinicalPhenotype

ClinicalPhenotype

0..1 identifiedEntity

typeCode*: <= SBJcontextControlCode: CS CNE [0..1] <= ContextControl "OP"

subject

reference


typeCode*: <= REFR

ObservedClinicalPhenotype

Note:This CMET might be replacedwith the Clinical Statement SharedModel for richer expressivity, whenthe that mode is approved(currently in ballot).

Constrained to a restricted BSMLcontent model, specified in aseparate schema.

Constraint: Sequence.value

0..* sequence

typeCode*: <= COMP

component4


typeCode*: <= COMP

component3

AssociatedPropertyclassCode*: <= OBSmoodCode*: <= EVNcode: CD CWE [0..1]text: ED [0..1]value: ANY [0..1]





typeCode*: <= COMP

component

AssociatedPropertyAssociatedObservation


typeCode*: <= DRIV

derivedFrom

AssociatedProperty0..* associatedProperty


AssociatedObservation0..* associatedObservation

typeCode*: <= COMPcomponent

0..* sequenceVariationtypeCode*: <= DRIV

derivedFrom3derivedFrom2

0..* sequence

typeCode*: <= DRIV


typeCode*: <= DRIV

derivedFrom4


typeCode*: <= DRIVderivedFrom


typeCode*: <= PERTpertinentInformation 0..* clinicalPhenotype


AssociatedProperty


typeCode*: <= DRIV

derivedFrom

AssociatedProperty

GeneticLociclassCode*: <= OBSmoodCode*: <= EVNid: SET<II> [0..*]code: CD CWE [0..1]effectiveTime: GTS [0..1]value: ANY [0..1]

0..* geneticLocitypeCode*: <= COMPcomponentOf



GeneticLoci

0..* geneticLoci

typeCode*: <= COMP

componentOf

GeneticLoci

0..* geneticLoci

typeCode*: <= COMP

componentOf

0..* polypeptide


Polypeptide

0..* polypeptide


Note:Use this class to indicate a set of genetic locito which this locus belongs. The loci set couldbe a haplotype, a genetic profile and so forth.Use the id attribute to point to the GeneticLociinstance if available. The other attributesserve as a minimal data set about the loci group.

PHENOTYPES

Note:Any observation related to the variation and is notan inherent part of the variation observation (the lattershould be represented in the AssociatedProperty class).For example, the zygosity of the variation.

Note:Use this class to point to a variationgroup to which this variation belongs.For example, a SNP haplotype.

Note:Any observation related to the sequence and is notan inherent part of the sequence observation (the lattershould be represented in the AssociatedProperty class).For example, splicing alternatives.

Note:Key peptides in the proteinthat determine its function.

Note:There could be zero to manyIndividualAllele objects in aspecific instance. A typicalcase would be an allele pair,one on the paternalchromosome and one on thematernal chromosome.

Note:Use this class toshow an allelehaplotype like in HLA.

Note:Any observationrelated to theexpression assayand is not aninherent part ofthe expressionobservation.

Note:Use this class forinherent dataabout the locus, e.g.chromosome no.

IdentifiedEntityclassCode*: <= IDENTid: SET<II> [0..*]code: CE CWE [0..1] <= RoleCode

Note:Use this role to identify a different subject(e.g., healthy tissue, virus, etc.) than theone propagated from the wrappingmessage or payload (e.g., GeneticLoci).

ScopingEntityclassCode*: <= LIVdeterminerCode*: <= INSTANCEid: SET<II> [0..*]code: CE CWE [0..1] <= EntityCode

0..* assignedEntity

typeCode*: <= PRFcontextControlCode: CS CNE [0..1] <= ContextControl "OP"

performer

0..*

performer

0..*

performer1

0..*

performer2

0..*

performer1

0..*performer2

Genetic Locus(POCG_RM000010)

The entry point tothe GeneticLocus modelis any locus on the genome.

Constrained to a restricted MAGE-MLcontent model, specified in aseparate schema.

Constraint: Expression.value

Expression

Sequence

SequenceVariation

SequenceVariation

0..* clinicalPhenotypetypeCode*: <= PERTpertinentInformation

ClinicalPhenotype

CMET: (ASSIGNED) R_AssignedEntity


0..1 scopedRoleName

CMET: (ACT) A_SupportingClinicalInformation


Longitudinal Patient EHR(RIM-based CEN 13606 EHR)

A Clinical Genomics Instance

Don’t leave behind the raw genomic data…

bring it into the EHR!

Amnon Shabo, IBM Haifa Research Lab

8

The Underlying Paradigm: Encapsulate & Bubble-up

Clinical GuidancePatient Genotype

EHR System

HL7 CG Messages

Encapsulating HL7 Objects

HL7 C

G m

essa

ges

asso

ciat

ed w

ith

HL7 c

linic

al o

bjec

ts (p

heno

type

s –

War

farin

met

abol

ism

)

Bubble up the most clinically-significant raw

genomic data into specialized HL7 objects and

link them with clinical data from the patient EHR

Decision Support Applications

Knowledge(KBs, Ontologies, registries,

reference DBs, Papers, etc.)

Bridging is the challenge…

Encapsulation of CYP2C9 and

VKORC1 sequence data

Evidence-based algorithm to

determine starting dose


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American Health Information Community Workgroups

The EHR Workgroup has identified ten priorities that represent essential minimum features or functions of EHRs. These features or functions are the utilities identified as the most important clinical data elements by clinicians who are either considering adoption of EHRs, or those who have adopted but desire interoperability in these areas. These utilities are noted in priority order as determined by the EHR Workgroup, and are all considered critical for comprehensive patient care.

1. Patient Identification2. Medication List / Allergy3. Laboratory Results4. Problem List5. Clinical / Encounter Notes6. Anatomic Pathology Results7. Vital Signs8. Family History/ Health Factors9. Radiology Reports: Not including images10. Immunizations

8. Family History/ Health Factors: May contain a detailed problem list and health history of a patient’s family members. Typically used by providers when assessing familial risk and planning care.

10

HL7 Clinical Genomics

Family History

Interoperability

PartnersFHCaGene

CDC/SurgeonGeneral

Any pedigreeprogram

trans

formtransform

transform transform

Ontologies:Clinical Genomics Knowledge

Query

ClinicalLab

GeneticLab

Search

Raw genomic

data

EHR:Patient data

&care goals

HL7 Lab

Message

user


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Implementations

• Family History– Massachusetts General Hospital– Fully based on the v3 models

• Incorporating genomic information into the patient EHR– Partners HealthCare – Structured reporting of sequencing

based genetic tests– Clinical decision support rules to leverage genetic tests results

• Genetic testing information exchange– Harvard HPCGG and Intermountain Health Care– Map to HL7 v2 lab messages that are currently supported by

existing lab systems on both sides

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For More Information

• For the Genetic Locus, Genetic Loci, and Family History model walkthroughs and XML Schemas, go to http://hl7.org/Special/committees/clingenomics/docs.cfm

• We encourage organizations to participate in HL7 to test the clinical genomic models (including AHIC to help advance implementation!)

• Send any further questions to Amnon Shabo, Co-Chair HL7 Clinical Genomics Special Interest Group, IBM Research Lab in HaifaE-mail: [email protected]

• Find HL7 website at www.hl7.org

• Contact me at via e-mail at [email protected]

Documents

1 Intermountain Healthcare Clinical Genetics Institute Marc S. Williams, M.D. Director Grant M. Wood Senior IT Strategist Introduction to HL7 Clinical